Transcriptional Elongation is Important for Neural Crest Development

Neural crest cells are a multipotent cell population, which migrate from the dorsal neural tube in early vertebrate development throughout the embryo to form a variety of cell types including pigment cells, craniofacial cartilage and sensory neurons [1, 2]. Here I show that the small molecule compound leflunomide is able to inhibit neural crest specification genes. Leflunomide exerts its actions by inhibiting pyrimidine synthesis and therefore RNA transcription [4]. Neural crest genes are thought to be actively transcribed and like many embryonic stem cell genes may undergo an increased level of transcriptional pausing and subsequent elongation rendering them more sensitive to the effect of leflunomide [3, 5]. I have gone on to show that components of the transcriptional elongation regulatory machinery, Cdk9 and CyclinT1 of the P-TEFb complex are also able to regulate neural crest specification. In particular the expression of the protooncogene c-Myc and c-Myc responsive genes are affected. c-Myc has been previously implicated in embryonic stem cell transcriptional elongation and also is well characterised to play a role in neural crest specification [6]. We postulate that regulation of c-Myc expression at the level of transcriptional elongation is important for the correct temporal and spatial development of the neural crest